2-p-methoxybenzenesulfonamide-5-isobutyl-1, 3, 4-thiadiazole in the oral treatment of acne



United States Patent No Drawing. Filed Nov. 6, 1959, Ser. No. 851,271 3Claims. (Cl. 167-55) This invention relates to an improved method in thetreatment of acne particularly pustular acne, and more particularly tothe treatment of acne by means of an orally ingested thiadiazole, moreparticularly 2-p-rnethoxyb enzenesulfonamide-S-isobutyl- 1 ,3 ,4-thiadiazole.

In severe cases of acute pustular acne, local therapy alone is of littlevalue. The specific systemic measures usually employed in addition tolocal therapy depend upon the seriousness of the skin condition.Additional measures which have been used in the past include: hormonetherapy, particularly diethylstilboestrol; dietary control; vitaminsupplements, particularly vitamin A and vitamin C; ultraviolet and X-raytherapy; administration of toxoids and vaccines; and use of antibiotics,such as sulfonamides; pencillin, erythromycin, chloramphenicol,oleandomycin, tetracycline and novobiocin. Isoniazid has also been used.Most consistent results have been achieved with chloramphenicol anderythromycin. Nevertheless, treatment with antibiotics is unsatisfactorysince, while a favourable response to usually obtained, this is followedby a new flare-up, and relapses are frequent after discontinuance of theantibiotics. The other forms of drug therapy are also not completelyeffective.

In pending application Serial Number 824,176 filed in the name of I. L.Cohen on July 1, 1959, now US. Patent No. 3,072,527, there is disclosedan improved method for the treatment of acne by the administration oftolbutamide. The utility of tolbutamide in the treatment of acne isunexpected, since tolbutamide has no bactericidal effect.

However, it is known that a 1.0 g. dosage of tolbutamide lowers bloodsugar levels about in normal individuals. While this lowering of theblood sugar is not serious, there may be cases where acne is to betreated when such lowering of blood sugar levels may be critical.

It is an object of the present invention to provide an improved oraltherapy for the relief of symptoms of acne.

This object is achieved in the method of treating acne which comprises:selecting a human having acne; and feeding said human a therapeuticallyeffective dose of2-pmethoxybenzenesulfonamide-S-isobutyl-1,3,4-thiadiazole.

Usually, the therapy consists in the ingestion, by the patient sufferingfrom acne, of tablets containing the thiadiazole. Although doses of 2-3grams per day of the thiadiazole may be safely used, effective doseswill be in the range of 0.5-1.0 gram per day.

A convenient form of treatment is the use of tablets containing fromabout 250 mg. to about 1000 mg. of the 2 p methoxybenzenesulfonamide-S-isobutyl-l,3,4-thiadiazole, with an especially convenientamount being 500 mg. of the thiadiazole per tablet. Preparation of suchtablets is given below.

EXAMPLE I.TABLETS The following proportions of ingredients were used:

Orange colored starch 6.5 Sodium bicarbonate 3.1 Magnesium stearate 0.8

The orange colors were dissolved in a granulating solution consisting ofa 24% solution of gelatin and acacra in water. The thiadiazole was thengranulated with 1.0 gm. of the colored starch, the amount of granulatingsolution originally used being suflicient to result in a dry granulationprocedure. The balance of the starch, the sodium bicarbonate and themagnesium stearate were then intimately mixed therewith and the mixturewas compressed into tablets.

The proportions used were sufiicient to result in the preparation of 100tablets, each weighing 620 mg. and containing 500 mg. of thethiadiazole.

EXAMPLE ILL-CAPSULES In this case 50.0 gm. of2-p-methoxybenzenesulfonamide-5-isobutyl-l,3,4-thiadiazole wasintimately mixed with 1.0 gm. of a light mineral oil. 100 capsules eachcontaining 500 mg. of the thiadiazole were then prepared by placing 510mg. of that mixture into hard gelatin capsules.

A series of patients were treated withZ-p-methoxybeuzenesulfonamide-S-isobutyl-1,3,4-thiadiazole according tothe method of the present invention. The results are tabulated in TableI below.

Table 1 Treatment with 2p-methoxybenzenesulfonamide-5-is0butyl- N 0Diagnosis Prior 1,3,4-thiadiaz0le Treatment Side Effects Evaluation 1..Cystic acne, Antivaccine None after 64 Good; patient recurringprogesterdays. free of acne iurunculoone, antitype of insis. biotics X-faction, feels ray, cryobetter. therapy.

2 Furunculo- Antibiotics... None after 89 Good; furunsis, relapsdays.cles have mg. not relapsed.

3 Furunculo- Antibiotics 54 days Good; pussis. antivaccine treatments.tules dried serum up quickly. globulin.

4....-. Severe cystic Progesterone None after 101 Good; appears acne.serobacteridays. to prevent um 00; outbreak of slush. new cystspremenstrually.

5"--. Furunculo- Antibiotics, None after 90 Good.

sis. vaccine. days.

6 Cystic acne. None None after 42 Slow steady days. improvement.

It is seen from the above table that2-p-methoxybenzenesnlfonamide-S-isobutyl-1,3,4-thiadiazole is efiectivein the treatment of acne.

The eflect of 2-p-methoxybenzenesulfonamide-S-isobuty11,3,4-thiadiazoleon the blood sugar of normal non- Table II 3000 mg. Z-p-methoxybenzene-Hours after sulfonamide-fi-isobutyl- 50 ggfi ingestion 1,3,4-th1admzoleNumber weight tolbutam 7 8 9 ide 100 100 100 100 s--. 56 100 97 95 68 t72 93 100 I 70 72 c 56 93 100 79 It will be seen from Table II thatWhile tolbutamide causes a rapid and substantial drop in blood sugarlevels at dosage levels of 50 mg./kg. body weight,2-p-methoxybenzenesulfonamide-S-isobutyl-1,3,4-thiadiazole, in themajority of cases, causes no significant decrease in blood sugar atapproximately the same dosage (3 grams total). It is also to beemphasized that the dose of tolbutamide with which the results of thepresent invention are compared is 50 mg./kg.

I claim:

1. The method of treating acne which comprises orally administering to ahuman affected with acne a daily dose of 0.5-3.0 grams, in individualdoses of 250-1000 mg. of 2 p methoxybenzenesulfonamide 5isobutyl-l,3,4-thiadiazole.

2. The method of claim 1 wherein the thiadiazole is fed in a dosage unitform containing about 0.5 gm. of said thiadiazole.

3. The method of claim 2 wherein the thiadiazole is fed in tablet form.

References Cited in the file of this patent Wortis: JAMA, 108112, March20, 1937, p. 971.

Lessor: Drug and Cos. Ind, 63:4, October 1948, pp. 466-468, 544-547.

Meshard: Prods. Pharm., vol. 13, October 1958, pp.

Bulletin Johns Hopkins Hospital, 85(3), pp. 221-230,

20 September 1959.

1. THE METHOD OF TREATING ACNE WHICH COMPRISES ORALLY ADMINISTERING TO AHUMAN AFFECTED WITH ACNE A DAILY DOSE OF 0.5-3.0 GRAMS, IN INDIVIDUALDOSES OF 250-1000 MG. OF 2 - P - METHOXYBENZENESULFONAMIDE - 5 -ISOBUTYL-1,3,4-THIADIAZOLE.